DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response filed on 12/24/2025 is acknowledged and fully considered.
Status of Application, Amendments, And/Or Claims
The amendments of claim 1 and the cancellation of claims 11-12 have been made of record.
Claims 1-10 and 13-15 are pending and under consideration.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/18/2025 has been considered.
Response to Arguments
Claim Rejections - 35 USC § 112-withdrawn
The rejection of claims 1-15 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification does not reasonably provide enablement for a method of preventing obesity or non-alcoholic fatty liver disease (NAFLD) comprising administering a composition to a subject in need thereof, wherein the composition comprises a long-acting conjugate of a triple agonist of Formula I (X-L-F) having activities to all of a GLP-1 receptor, a GIP receptor and a glucagon receptor is withdrawn in view of applicant’s amendments to claim 1 to delete the term “preventing”.
Claim Rejections - 35 USC § 102-withdrawn
The rejection of claim(s) 1-3, 6-9, and 14 under 35 U.S.C. 102(a)(1) as being anticipated by Oh et al. (US Pub. No. 2018/0311315) is withdrawn in view of applicant’s amendments of claim 1 to incorporate the limitation of claim 12.
Claim Rejections - 35 USC § 103-withdrawn
The rejection of claim(s) 1-10 and 14-15 under 35 U.S.C. 103 as being unpatentable over Oh et al1. (US Pub. No. 2018/0311315) in view of Oh et al2. (US pub. No. 20140357843 A1), Choi et al (IDS, Diabetes 2019, 68 (supplemental): 982-P) is withdrawn in view of applicant’s amendments of claim 1 to incorporate the limitation of claim 12.
Claim Rejections - 35 USC § 103-maintained
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-10 and 13-15 remain rejected under 35 U.S.C. 103 as being unpatentable over Oh et al1. (US Pub. No. 2018/0311315) in view of Oh et al2. (US pub. No. 20140357843 A1), Choi et al (IDS, Diabetes 2019, 68 (supplemental): 982-P) and Oh et al3 (US Pat. No. 10,400,020) necessitated by applicants’ amendments to claim 1 and the cancellation of claims 11-12.
The instant claims are broadly drawn to a method of preventing or obesity or non-alcoholic fatty liver disease (NAFLD) comprising administering a composition to a subject in need thereof, wherein the composition comprises a long-acting conjugate of a triple agonist of Formula I (X-L-F) having activities to all of a GLP-1 receptor, a GIP receptor and a glucagon receptor, wherein X is selected from a SEQ ID NO: 21,22,31,32,37,42,43,50, 53, …, 101 and 102, L is a linker and F is an Fc , wherein the composition comprising triple agonist is administered once a week at dose of 2 mg to 6 mg (claim 2), wherein the administration is subcutaneous (claim 3), wherein the patient has BMI 23 kg/m2 or higher (claim 4), wherein the patient administered with the pharmaceutical composition exhibits weight loss (claim 6), wherein the pharmaceutical composition is administered to an arm, thigh, or abdomen (claim 7), wherein the F is an IgG Fc region (claim 8), wherein the polypeptide chain of the Fc dimer includes an amino acid sequence of SEQ ID NO: 123 (claim 10), wherein the L is polyethylene glycol having a molecule (claim 14), and wherein the non-alcoholic fatty liver disease is selected from the group consisting of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and any combination thereof.
Oh et al. teach a method of treating obesity, reducing body weight and body fat comprising a long-acting conjugate of a triple agonist of Formula I (X-L-F) having activities to all of a GLP-1 receptor, a GIP receptor and a glucagon receptor. They teach amino acid sequences of X from SEQ ID NO: 1-102 (see Table 1), wherein SEQ ID No. 1 of Table 1 is 100% identical to the instantly claimed sequence of SEQ ID NO: 1. They teach administering a triple agonist to high-fat diet induce obesity mice, which were widely used obesity model [0570]. They administered 2.88 nmol/kg injection once every two days using triple agonist resulting 56-65% reduction in body weight (see [0572], Fig. 1). They teach that the administration can be 0.0001 mg to 500 mg/kg depending on disease severity [0541]. They teach that the pharmaceutical composition can be formulated to be administered parenteral route, such as intravascularly or subcutaneously [0538]. They teach that a patient having obesity has BMI is 25 or higher [0531]. They teach that the administration of triple agonist resulted in significant decrease in body fat (see Fig. 2). They teach that L is linker that which is polyethylene glycol (see claim 22). They teach that the Fc is an IgG Fc (see claim 19) and that the molecular weight of non-peptide linker can be 1-20 kDa (see [0482]).
Oh et al. do not teach a patient with NAFLD having fat content 8% or more measured by magnetic resonance imaging-derived proton density fat fraction, wherein the long-acting conjugate has the Fc region as a dimer form of two polypeptide chains and the peptide X is linked to only one of the two polypeptide chain of the Fc dimer, wherein the Fc dimer includes an amino acid sequence of SEQ ID NO: 123, wherein the X includes an amino acid sequence selected from the group consisting of SEQ ID NO: 40,43 and 50, and wherein the NAFLD is selected from the group consisting of NASH, liver fibrosis, cirrhosis, and combination thereof.
Oh et al2. teach immunoglobulin Fc variants having an increased binding affinity for FcRn and a method of increasing in vivo half-life of a physiologically active protein using the same (see [0001]).They teach an Fc of SEQ ID NO: 73 which is 100% identical to the instantly claimed Fc amino acid sequence of SEQ ID NO: 123 (see sequence search results #1 of 55 identical sequences in PE2E).
Choi et al. (IDS, Diabetes, 2018: 67(supplemental) 1106-P) teach that NASH, a potential consequence of NAFLD, may lead to end stage liver disease including cirrhosis and hepatocellular carcinoma. They teach use of HM15211 a novel triple agonist (GLP-1/GIP/glucagon) for NASH. They teach that the treatment with triple agonist led to significant decrease in hepatic Triglyceride (TG) (-82% vs vehicle). They suggest that the triple agonist offers a potential for NASH and fibrosis as well as obesity.
Neither Oh et al1., Oh et al2. nor Choi et al. teach X polypeptide having amino acid sequence of SEQ ID NO: 42.
Oh et al3 . teach a triple agonist (glucagon, GLP-1 and GIP) receptors having formula I ( X-L-F), wherein X is a polypeptide, L is a linker and F is a polypeptide that increases the half-life of the composition. Oh et al3 . teach that the polypeptide X comprises amino acid sequence of SEQ ID NO: 42 is which is 100% identical to the instantly claimed X peptide of SEQ ID NO:42 (see search result #2 of 7 identical sequences in PE2E). They teach a total of 102 polypeptide X sequence which are similar to the X peptide sequences taught in the instant application.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to treat NASH or fibrosis using a triple agonist (GLP-1/GIP/glucagon) as taught by choi et al wherein the triple agonist comprises an Fc comprises amino acid sequence of SEQ ID NO: 123 as taught by Oh2 et al. in the Formula I (X-L-Fc) as taught by Oh1 et al. and wherein X is amino acid sequence of SEQ ID NO: 42 as taught by Oh et al3 . Additionally, one would have been motivated to do so because Choi et al teach treating NASH, obesity or fibrosis using a triple agonist (GLP-1/GIP/glucagon) and Oh1 et al. teach treating obesity using a triple agonist of Formula I (X-L-F) wherein X is a triple agonist peptide and F is an Fc which is well known to stabilize any physiologically active polypeptide also taught by Oh2 et al. and Oh et al3 teach that X comprises amino acid sequence of SEQ ID NO:42, Further, one would have a reasonable expectation of success in using a triple agonist for treating NASH, obesity or fibrosis as taught by Choe et al. wherein the agonist comprises Formula I as taught by Oh1 et al. It is also well known in the art and as taught by Oh2 et al. to use an Fc having amino acid sequence of SEQ ID NO: 123 because it increases the binding affinity for FcRn and increases in vivo half-life of a physiologically active protein. Therefore, the instantly claimed invention would have been obvious over the combined teachings of prior art.
Applicants argue that Oh discloses the same triple agonist as set forth in claim 1 but they disclose a broad range of dose in the range of 0.0001-500 mg/kg, whereas the instant claims require a specific dose 0.5 mg to 8 mg once a week. They argue that the working example of Oh used administration of the dose once every two days. They argue that pharmaceuticals require clinical trials during develop to establish dosage, administration regimen, safety and efficacy and that such trials involve large-scale resources, costs and time, unlike laboratory experiments and thus dosage and administration cannot be derived through routine experimentation. Additionally, regarding administering to patient with non-alcoholic fatty liver disease, they argue that Oh is directed to different patient population.
Applicants’ arguments have been fully considered but they are not persuasive because the dose suggested by Oh 2.88 nmol/kg once every two days or in a range of 0.0001-500 mg/kg depending on disease severity provides sufficient guidance to one ordinary skill in the art to determine appropriate dosage and time for treating a specific subject population. The state of the skill using GLP-1 related triple agonist for reducing body weight and body fat. Regarding applicants’ arguments that dosing and frequency requires a large scale trial is needed for determining efficacy of a drug have been fully considered but they are not persuasive because the claims do not require a particular efficacy of the drug or a large scale clinical trial for determining a dosage range.
“Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." See In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989); see also MPEP §716.02(c). Additionally, “[it] is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and MPEP § 2144.06.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
a. Claims 1-8, 11-13 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 15-24 of U.S. Patent No. 10,400,020 for the reasons of record at pg. 12-15 of the office action of 9/24/25.
Claims 1-8 and 11-15 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 15-24 of U.S. Patent No. 10,400,020 in view of Choi et al (IDS, Diabetes 2019, 68 (supplemental): 982-P) for the reasons of record at pg. 15 of the office action of 9/24/25.
Claims 1-8 and 11-13 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 9-13, 14, 17-20, 29, and 35-36 of U.S. Patent No. 10,981,967 for the reasons of record at pg. 16 of the office action of 9/24/25.
Claims 1-8 and 11-15 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/016,165 (reference application) for the reasons of record at pg. 16 of the office action of 9/24/25.
Claims 1-8 and 11-15 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-41 of copending Application No. 18/041,151 (reference application) for the reasons of record at pg. 16-17 of the office action of 9/24/25.
Claims 1-8 and 11-14 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/565,628 for the reasons of record at pg. 17-18 of the office action of 9/24/25.
Applicant traverses and requests that the rejections be held abeyance until at least one allowable claim is identified.
Applicant’s arguments have been fully considered but they are not persuasive because the Double patenting rejection is made under separate statute and therefore, they are maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/GYAN CHANDRA/ Primary Examiner, Art Unit 1674